Background and importance A prescribing cascade (PC) is defined as the misinterpretation of an adverse drug event (ADE) from one medication (index medication) as a medical condition, which is subsequently treated with another medication (marker). A PC is problematic when the benefits of this combination of medication do not outweigh the risks on the patient’s health. PCs have been described previously, but unawareness remains amongst pharmacists. The average length of stay in hospitals has decreased, which results in PCs where the index medication is initiated in the hospital and the ADE is treated in primary care.

Aim and objectives For this reason, we aimed to quantify the occurrence of problematic PCs using community pharmacy records.

Material and methods A mixed-methods study was conducted to compose a list of problematic PCs relevant for the Netherlands, including a literature review and an assessment by 16 experts (pharmacists and physicians in hospitals and primary care). Next, a retrospective cohort study using the Prescription Sequence Symmetry Analysis (PSSA) method was performed to quantify PCs. Data were extracted from 656 community pharmacies from 2015 until 2020. The PSSA method evaluates the asymmetry in the distribution of the prescription of the marker medication before and after the prescription of the index medication. An adjusted sequence ratio (aSR) was calculated to adjust for prescribing trends over time. An aSR ≥1 indicates an increased probability of an index medication followed by a marker medication. Data were analysed using SPSS version 22.

Results Experts assessed 90 PCs from literature, and 59 were categorised as problematic PCs. These PCs mostly concerned antidepressants, antipsychotics and lipid-modifying agents as index medication. Depression, erectile dysfunction and urinary incontinence were the most frequently occurring ADEs. A significant aSR was found for 37 (63%) of 59 PCs. For 16 PCs the aSR was between 1 and 1.5 and for 21 the aSR was >1.5. The highest aSR was 4.28 (95% CI 4.08 to 4.49) for amiodarone, followed by thyroid hormones, based on 654 incident users.

Conclusion and relevance In this study 37 (63%) of 59 problematic PC had a significant positive association when quantified. This illustrates that more awareness is needed by pharmacists to prevent PCs.

Conflict of interest Corporate sponsored research or other substantive relationships: KNMP and Ncontrol.